Endocrine Abstracts

A 69-year-old woman was referred from primary care to Endocrinology in December 2024 with apparent new onset Type 2 Diabetes Mellitus, associated with a rapid deterioration in HbA1c which increased from 21 mmol/mol Hb (July 2023) to 51 mmol/mol Hb (March 2024). Relative inactivity, following a DVT in March 2024, was considered a possible contributor. However, this was not associated with weight gain nor any other remarkable clinical or laboratory findings. Although the HbA1c analyser changed (from Menarini to Array) over this period, the same methodology (cation exchange HPLC) was used, both demonstrating comparable analysis. Furthermore, a variant Hb (Peak D) was consistently detected by both HbA1c analysers. However, HbA1c levels and trending were discordant to fasting glucose (6.9 mmol/l [July 2023]; 5.5 mmol/l in March 2024) and to HbA1c analysed by different methodology (Boronate Affinity HPLC: 38 mmol/mol, Latex immunoagglutination inhibition: 37 mmol/mol). Fructosamine (247 umol/l) was within reference limits (205-285 umol/l), equivalent to HbA1c < 42 mmol/mol Hb, corroborating glucose and latter HbA1c analysis. Interestingly, HbA1c could not be determined by Capillary Zone Electrophoresis due to presence of an unknown alpha variant (heterozygote). Our case illustrates the unreliability of HbA1c analysis in the presence of Hb variants, of which >900 exist and are of increasing prevalence as our population diversifies. We call upon laboratories to not only (“passively”) caution and advise clinicians regarding alternative and more appropriate methods of long-term glycaemic assessment, where such variants are identified, but to also actively reflex for such testing where possible.